Poly-microbial Clostridium cadaveris bacteremia in an immune-compromised patient

ABSTRACT Clostridium cadaveris (C. cadaveris), a strict anaerobic gram-positive rod, is rarely reported in clinical specimens. Since its detection in 1899, it has always been linked to the decay of dead bodies. C. cadaveris is considered non-pathogenic to humans, however infrequently it can cause severe infections including bacteremia. The latter was typically associated with gastro-intestinal pathologies. We report the first case of C. cadaveris invasive infection at Sultanate Oman. The source was most probably an infected decubitus ulcer.


INTRODUCTION
Clostridium cadaveris is a motile, slender-shaped, ubiquitous, anaerobic, gram-positive rod bacterium. It was first identified by Klein et al. in 1899, where it grew from rotting corpses [1]. In fact, C. cadaveris is one of the prominent bacteria that grow during the decay of dead bodies. It is considered one of the normal human gastro-intestinal (GI) f lora, but it can occasionally cause severe infections.
Herein, we report a case of an elderly woman with a history of breast cancer on hormonal therapy and locally advanced left shoulder myxo-fibrosarcoma on local radiotherapy, who presents with septic shock caused by an infected decubitus ulcer. She was found to have poly-microbial bacteremia where blood cultures grew C. cadaveris, Proteus mirabilis and Staphylococcus hominis. The patient responded well to intravenous (IV) antimicrobial therapy and bedside debridement.

CASE REPORT
A 72-year-old female patient with a history of hypertension, aortic stenosis post aortic valve replacement and dual malignancies of breast cancer on hormonal therapy and locally advanced shoulder myxo-fibrosarcoma on radiotherapy, presents to Sultan Qaboos University Hospital (SQUH) for hypotension and fever of one day's duration. The physical examination was remarkable for an infected sacral decubitus ulcer; stage IV ( Fig. 1A). Her labs on admission showed a white count of 19.3 x 10 9 cells per liter with 92% neutrophils and 5% lymphocytes. Her C-reactive protein (C-RP) level was 207 mg/dl. She underwent a pelvis computed tomography (CT) with IV contrast, which showed fat stranding with air locules at the level of the sacral ulcer; however, it was negative for deep collections or osteomyelitis (Fig. 2). She was started empirically on meropenem 1 gram (gm) IV Q 8 hours plus vancomycin 1 gm IV Q 12 hours.
One set of blood cultures grew C. cadaveris and S. hominis, detected after 48 hours by using Matrix-assisted laser desorption/ionization-time of f light (MALDI-TOF) and the VITEK 2 automated system, respectively. The cut-off score of MALDI-TOF was 1.9, thus a repeat of speciation was done, that showed again C. cadaveris with the same score. The C. cadaveris isolate was susceptible to metronidazole with a minimum inhibitory concentration (MIC) of 0.032 detected by E test method. The isolate of S. hominis was susceptible to oxacillin with an MIC of 0.25. A deep swab culture from the decubitus ulcer grew P. mirabilis, which was susceptible to cefotaxime with an MIC < 1. She was, therefore, shifted to ceftriaxone 2 gm IV once daily plus metronidazole 500 mg IV Q 8 hours. The presence of prosthetic valve warranted the need to rule out the possibility of persistent bacteremia and endocarditis. For that, a third set of blood cultures and a TTE were done. The repeated blood culture grew P. mirabilis, with a similar susceptibility pattern as the previous isolate. The TTE result was unremarkable. Beside this, a bedside debridement and vacuum dressing was done by the wound care team. After 10 days of IV therapy, her white cell count dropped to 11 000 x 10 9 cells per liter. Her C C-RP level decreased to 52 mg/dl. The patient was discharged on Amoxicillin-Clavulanate 1 gm bid for extra 1 week.

DISCUSSION
Clostridium bacteremia contributes only 0.5-2% of total bacteremia [2]. It's usually associated with GI pathologies. In fact, the disruption of the GI epithelium due to any pathology was found to be the main factor leading to Clostridium species bacteremia [3]. Furthermore, it is associated with a myriad of risk factors, including: malignancy, immune-suppression, poor physical condition, diabetes mellitus, decubitus ulcer, steroid therapy and chemotherapy [3]. In our case, the patient had a dual malignancy of breast cancer and myxo-fibrosarcoma, albeit she was not on an active chemotherapy regimen.
Although scarcely reported in the literature, C. cadaveris was found to be the causative microorganism to several severe infections including septic arthritis, lung empyema, peritonitis, splenic abscess, osteomyelitis and bacteremia [4][5][6][7][8]. There are only eight cases of C. cadaveris bacteremia in the literature ( Table 1). The source of the infection in the reported cases was mostly the GI system. In our case, the potential source was the infected decubitus ulcer; especially that P. mirabilis grew on both wound and blood cultures. The inability to isolate C. cadaveris on the wound culture can be justified by the need for special handling when dealing with tissue or wound cultures. Also, the presence of enriched media in blood cultures may help in detecting such difficult to isolate micro-organism. To our knowledge, there is only one previous report with the same source of infection [3].
From the microbiology perspective, C. cadaveris can be identified by standard methods including API system, MALDI-TOF, Vitek 2 and 16 S rRNA sequencing [10,12,13]. MALDI-TOF is considered a proven useful method in detecting anaerobic organisms at the genus and species levels with a correct identification rate of at least 92% and 70%, respectively [12,13]. For correct identification, the MALDI-TOF's manufacturer recommended a cutoff score of 2, however Schmitt et al. showed that lowering the score value to 1.8 would increase the species-level identification from 70% to at least 85% [13]. In fact, other studies showed similar results, where cutoff score of 1.8 was recognized to increase the correct identification [14,15]. C. cadaveris is usually susceptible to Metronidazole, which is considered the first line therapy [10]. Back to our patient, she received a total of 14 days of IV antimicrobial therapy in addition to bedside debridement, with a good response (figure 2). She was discharged on amoxicillin/clavulanate per os (PO) for an extra 1 week.
In summary, C. cadaveris bacteremia is extremely rare, where it mainly occurs in patients with GI pathology. Other main risk factors include malignancy, immune-suppression, chronic debilitating status, decubitus ulcers and diabetes mellitus. The report highlights the importance of anaerobic blood cultures and the role of MALDI-TOF in increasing the detection yield of the anaerobic bacteria.

AUTHORS' CONTRIBUTION
Dr Bassem Awada and Dr Jorge Abarca contributed equally to writing the manuscript, literature review and revision of the manuscript. Dr Boris contributed to writing the manuscript. Dr Manyando Mulipi contributed to writing the manuscript and data analysis.